Dact gene expression profiles suggest a role for this gene family in integrating Wnt and TGF‐β signaling pathways during chicken limb development

Abstract

Background: Dact gene family encodes multifunctional proteins that are important modulators of Wnt and TGF-b signaling pathways. Given that these pathways coordinate multiple steps of limb development, we investigated the expression pattern of the two chicken Dact genes (Dact1 and Dact2) from early limb bud up to stages when several tissues are differentiating. Results: During early limb development (HH24-HH30) Dact1 and Dact2 were mainly expressed in the cartilaginous rudiments of the appendicular skeleton and perichondrium, presenting expression profiles related, but distinct. At later stages of development (HH31-HH35), the main sites of Dact1 and Dact2 expression were the developing synovial joints. In this context, Dact1 expression was shown to co-localize with regions enriched in the nuclear b-catenin protein, such as developing joint capsule and interzone. In contrast, Dact2 expression was restricted to the interzone surrounding the domains of bmpR-1b expression, a TGF-b receptor with crucial roles during digit morphogenesis. Additional sites of Dact expression were the developing tendons and digit blastemas. Conclusions: Our data indicate that Dact genes are good candidates to modulate and, possibly, integrate Wnt and TGF-b signaling during limb development, bringing new and interesting perspectives about the roles of Dact molecules in limb birth defects and human diseases. Developmental Dynamics 243:428-439, 2014. V C 2013 Wiley Periodicals, Inc.Key words: Dact; Dapper; Frodo; chicken embryo; Wnt; TGF-b; limb; chondrogenesis; appendicular skeleton; Sox9; cartilage; perichondrium; joint; digit blastema; tendon; digit morphogenesis; limb evolution Key findings:Dact1 and Dact2 are dynamically expressed during early chondrogenesis in sites that either overlap or complement Sox9 expression domains. Dact1 and Dact2 are coexpressed in developing joints, tendons, and digit blastemas. Dact1 mRNAs colocalize with nuclear b-catenin protein while Dact2 complements sites of bmpR-1b expression in developing synovial joints of digits.

Dactgenes are chordate specific regulators at the intersection of Wnt and Tgf-β signaling pathways

“…Dact2 showed prominent expression in young somites and the developing intestine (Figure 5 A-C; [ 27 ]); in more strongly stained specimen, all somites as well as the trigeminal, facial and glossopharyngeal ganglia were labeled (not shown). Chicken Dact1 was expressed in the presomitic mesoderm and young somites, the craniofacial mesenchyme, the splanchnopleural lateral mesoderm, several cranial ganglia and the epibranchial placodes (Figure 5 D; [ 27 ]); expression in the mature somites, in the limb mesenchyme and the dorsal root ganglia emerged slightly later at E3 ([ 27 , 31 ]. Chicken Dact2 is known for its early expression in the cranial neural crest [ 27 ].…”

“…At E2.5, the gene was expressed in the somites, the craniofacial mesenchyme, and several cranial ganglia (Figure 5 E; [ 27 ]). Later at E3, the gene was also expressed in the mesenchyme surrounding the dorsal root ganglia, the limb buds, the lung bud and the eye [ 27 , 31 ]. Xenopus dact1 expression was initially found in the dorsal blastopore lip, the neural plate, the emerging neural crest cells and the emerging paraxial mesoderm ([ 3 ] and not shown).…”

“…The embryos are at the phylotypic stage of vertebrate development; they were assayed for mRNA expression of Dact genes as indicated in the panel. Note that for members of both the Dact1/3 paralog group, as well as for the Dact2/4 paralog group, prominent expression was found in the paraxial mesoderm, craniofacial mesenchyme, pharyngeal arches and cranial ganglia as well as the developing paired limbs/ fins (for the chicken; this expression emerges at E3; [ 31 ]), suggesting that these are original sites of Dact function. At a number of sites, expression of Dact paralogs overlaps, suggesting that here Wnt and Tgfβ signal transduction is controlled by combinatorial Dact activity.…”

Sox9 Expression in Amniotes: Species-Specific Differences in the Formation of Digits

“…Sox9 is a well known marker of the skeleton that precedes the appearance of cartilage blastemas (Wright et al, 1995; Healy et al, 1999; Chimal-Monroy et al, 2003; Kawakami et al, 2005; Lorda-Diez et al, 2011; Sensiate et al, 2014). Hence, Sox9 is expressed even in domains that represent skeletal pieces lost in the course of evolution of specialized species (de Bakker et al, 2013).…”

MicroRNA‑214 promotes the proliferation, migration and invasion of gastric cancer MKN28 cells by suppressing the expression of Dact2

“…Dapper, antagonist of β-catenin (Dact) gene is a signal pathway regulating molecule that exerts its function by negatively regulating Wnt/β-catenin and Nodal/TGFβ signaling pathways (7,8). Wnt/β-catenin and Nodal/TGFβ signaling pathways participate in the regulation of the occurrence and development of tumors, and Dact gene can therefore play a role in the occurrence and development of tumors by affecting these signaling pathways (9). Dact2 gene is a member of Dact family that plays a role in tumors by participating in the negative regulation of both Wnt/β-catenin and Nodal/TGFβ signaling pathways (10).…”